Production of the HIV-suppressive chemokines CCL3/MIP-1alpha and CCL22/MDC is associated with more effective antiretroviral therapy in HIV-infected children

Abstract

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Background: Certain CC chemokines including ligands for the HIV-1 coreceptor CCR5 are associated with suppression of HIV-1 infection. Whether the release of these chemokines from lymphocytes influences treatment outcome in children receiving antiretroviral therapy is not known.

Methods: A study of 175 HIV-infected children in Rio de Janeiro, Brazil was conducted to compare clinical measures and HIV-suppressive chemokine release. Clinical measures including %CD4 T cells, viral loads, and antiretroviral drug-resistant mutations were obtained. Chemokine release was measured in cultures of peripheral blood mononuclear cells collected from 135 children before or after receiving therapy. Chemokine levels were compared between subject groups stratified according to clinical measures and treatment regimen (1-2, 3-4, or no antiretrovirals) extant at the time of cell sample collection.

Results: Mean viral loads did not vary significantly between treatment groups although there were significant differences in %CD4 T cells. Virus from children taking 3-4 antiretrovirals had significantly more drug-resistant mutations than did virus from those receiving 1-2 drugs. Among antiretroviral-treated children, there was a significant direct relationship between %CD4 T cells and MIP-1alpha/CCL3 and macrophage-derived chemokine/CCL22 production. In addition, there was a significant inverse relationship between viral load and MIP-1alpha production in patients receiving 3-4 antiretrovirals. Greater recovery of %CD4 T cells after therapy was associated with higher MIP-1alpha and macrophage-derived chemokine production at baseline.

Conclusions: The production of HIV-suppressive chemokines is associated with better outcome in children receiving antiretroviral regimens in settings where drug-resistant mutations are prevalent. Such information may provide insights for the design of treatment strategies for pediatric HIV infection under similar circumstances.